In the past, jugular bulb venous oximetry has been used to provide a global overview of the dynamic relationship between brain oxygen delivery and demand in certain acute neurological disorders. However, the invasive nature of this method as well as the lack of regional specificity have limited the scope of its application in clinical practice. It is critical important to be able to accurately assess and quantify the relationships between oxygen supply and oxygen demand on a regional basis, so that the pathophysiology of acute stroke and related disorders can be investigated. In this proposal, we will test the general hypothesis that the oxygen saturation of venous blood within the brain parenchyma can be measured, in absolute terms, using advanced magnetic resonance imaging (MRI) techniques. Specifically, the MR signal intensity changes induced by the presence of deoxyhemoglobin within the cerebral vasculature will be measured using a novel gradient/spin echo sequence. High resolution maps of regional cerebral blood volume (rCBV) will also be measured using a three-dimensional steady state MRI method. Combining information from these two imaging sequences, the oxygen saturation of blood within the brain parenchyma can be estimated. We will first validate the proposed MRI methods by testing their ability to accurately predict the oxygen saturation of blood within the brain parenchyma of the rat under a wide variety of pathophysiologic conditions. The validation process will be carried out using well established physiologic manipulations that produce global changes in cerebral blood oxygen saturation and rCBV. These will include acute hemorrhagic hypotension, hemodilution, alterations of arterial carbon dioxide tension, and hypoxemia. These experimental paradigms lend themselves to direct comparison with the gold standard used throughout the project-the oxygen saturation of jugular venous blood samples. Finally, well characterized rat models of focal ischemic injury will be used to investigate the regional applicability of the proposed methods. The success of this proposal should provide the opportunity to non- invasively measure the oxygen saturation of blood within the brain parenchyma on a regional basis with high spatial resolution. This capability could introduce a widely available means for monitoring the dynamic pathophysiology of altered oxygen delivery, and the brain's response to certain therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037312-04
Application #
6539965
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (06))
Program Officer
Pancrazio, Joseph J
Project Start
1999-02-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2004-12-31
Support Year
4
Fiscal Year
2002
Total Cost
$315,574
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
An, Hongyu; Ford, Andria L; Chen, Yasheng et al. (2015) Defining the ischemic penumbra using magnetic resonance oxygen metabolic index. Stroke 46:982-8
An, Hongyu; Ford, Andria L; Vo, Katie D et al. (2014) Imaging Oxygen Metabolism In Acute Stroke Using MRI. Curr Radiol Rep 2:39
Li, Yimei; Gilmore, John H; Shen, Dinggang et al. (2013) Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data. Neuroimage 72:91-105
Liu, Qingwei; Cai, Yu; Lin, Weili et al. (2012) A magnetic resonance (MR) compatible selective brain temperature manipulation system for preclinical study. Med Devices (Auckl) 5:13-22
An, Hongyu; Liu, Qingwei; Eldeniz, Cihat et al. (2011) Absolute oxygenation metabolism measurements using magnetic resonance imaging. Open Neuroimag J 5:120-35
Chen, Yasheng; An, Hongyu; Zhu, Hongtu et al. (2011) Longitudinal regression analysis of spatial-temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging. Neuroimage 58:993-1005
Li, Yimei; Zhu, Hongtu; Shen, Dinggang et al. (2011) Multiscale Adaptive Regression Models for Neuroimaging Data. J R Stat Soc Series B Stat Methodol 73:559-578
Skup, Martha; Zhu, Hongtu; Wang, Yaping et al. (2011) Sex differences in grey matter atrophy patterns among AD and aMCI patients: results from ADNI. Neuroimage 56:890-906
An, Hongyu; Liu, Qingwei; Chen, Yasheng et al. (2009) Evaluation of MR-derived cerebral oxygen metabolic index in experimental hyperoxic hypercapnia, hypoxia, and ischemia. Stroke 40:2165-72
Wu, Yang; An, Hongyu; Krim, Hamid et al. (2007) An independent component analysis approach for minimizing effects of recirculation in dynamic susceptibility contrast magnetic resonance imaging. J Cereb Blood Flow Metab 27:632-45

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